Final Report Summary - INNOVANTI (Innovative tools to examine the development of antisocial behaviour from early childhood to adolescence: Genetically informative designs and propensity score matching)

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Final Report Summary - INNOVANTI (Innovative tools to examine the development of antisocial behaviour from early childhood to adolescence: Genetically informative designs and propensity score matching)

Background and main objective. Antisocial behaviour represents a substantial problem in Europe. It is detrimental to the victims but also to the youth and families. It represents a burden on public finances. Among promising research avenues are the use of genetically informative longitudinal studies to better understand the developmental processes underlying antisocial behaviour as well as its environmental/genetic origins. This project aimed to implement such advanced longitudinal genetically informative designs to shed further light on the development of antisocial behaviour from early childhood to adolescence.

Cohort. To achieve this aim, we relied on the Twins Early Development Study (TEDS). TEDS is a longitudinal study of over 10000 pairs of twins born in England and Wales between 1994 and 1996 and representative of the UK population. Participants were followed from the age of 2 to 16 years. This study is one of the biggest existing longitudinal twin studies.

Main results and conclusions.

Genetic and environmental influences on developmental processes.

We focused on two childhood and adolescent behavioural problems – conduct problems and hyperactivity/impulsivity – as they represent components and/or precursors of antisocial behaviour. Conduct problems consists in behaviours such as fight/bully other children or steal from others and represent an early manifestation of antisocial behaviour. Hyperactivity/impulsivity includes behaviours such as not thinking before acting, not being able to stay still, and is an important precursor of antisocial behaviour.

These two studies on the TEDS sample included repeated measures of conduct problems and hyperactivity/impulsivity from age 4 to age 16 years. We implemented latent growth curve modelling, which is a statistical technique to model individual differences in the initial level of a behaviour (e.g. children that have higher or lower conduct problems at age 4 years) and the development of this behaviour over time (e.g. children who have increasing, stable or decreasing levels of conduct problems from age 4 to age 16 years). We then used twin modelling to investigate the genetic and environmental origins of individual differences in both the initial status as well as the developmental course of these two types of behavioural problems.

The results, published in JAMA psychiatry (2015) and Scientific Report (2015), highlighted the importance of genetic factors in explaining the long-term maintenance, decrease or increase in conduct problems and hyperactivity/impulsivity over time. Conversely, environmental influences appeared less important and/or short-term. Taken together, findings from this part of the project suggest that more advanced developmental models will be key in identifying genetic influences on childhood behavioural problems. They also suggest that one-time early preventive interventions are unlikely to be ‘magic bullets’. Instead, repeated efficient interventions at different developmental stages might be needed to counteract genetic propensity to develop behavioural problems. From a translational perspective, the findings suggest that the maintenance or increase in behavioural problems (i.e. hyperactivity and conduct problems) might represent a marker of vulnerability reflecting genetic liability and warrant a closer follow-up.

The structure of callous-unemotional trait

Recently callous-unemotional (CU) traits – a lack of empathy and guilt, as well as shallow affect – have emerged as a potential key predictor of antisocial behaviour. A Callous-Unemotional trait specifier (termed ‘Limited Prosocial Emotions’) was added to the diagnosis of conduct disorder in the DSM-5. The Inventory of Callous-Unemotional Traits (ICU) is a comprehensive measure of these traits assessing three distinct, yet correlated dimensions – Callousness, Uncaring, and Unemotional – all thought to reflect the general Callous-Unemotional construct. We were the first to examine the degree to which the aetiology of these dimensions is shared vs. Independent. The ICU was measured in TEDS at age 16 years.

The results showed that individual differences in a general factor representing CU traits could be explained by genetic influences (around 60%) as well as environmental influences (25% shared between twins and 15% specific to each twin). Interestingly, the results also showed that the distinction in three dimensions – Callousness, Uncaring, and Unemotional – was not adequate as Callousness and Uncaring were best represented as only one dimension and the usefulness of the Unemotional dimension could be put into question. These findings, published in Psychological Medicine (2015) have implications for future research aiming to refine measures of Callous-Unemotional traits. They also have implications for clinicians, as they suggest that it may be more beneficial to focus on the Callousness and Uncaring features when subgrouping youth with conduct problems.

Peer victimization and antisocial behaviour

Peer victimization (being bullied) is an important problem in childhood and adolescence. Among the potential adverse outcomes of peer victimization is an increase in later antisocial behaviour. However, it is difficult to establish whether the association between peer victimization and later antisocial behaviour is causal due to environmental and genetic confounding. This is because peer victimization does not occur at random: environmental influences (e.g. family socioeconomic status) as well as genetic influences (for example, as shown above, hyperactivity/impulsivity is heritable and impulsive children may be more susceptible to 'get into trouble' and be victimized, a phenomenon labelled gene-environment correlation) both contribute to peer victimization. It is crucial to use genetically-informative designs to better assess the influence of risk factors such as peer victimization on antisocial behaviour.

In this study, we used peer victimization at age 12 years in TEDS and antisocial behaviour at age 16 years. We used the discordant Monozygotic (MZ) twins design. MZ twins share 100% of their genetic material, which allows researchers to control for genetic influences when examining the effect of a risk factor (peer victimization) on an outcome (antisocial behaviour). Results confirm genetic influences on peer victimization and that most of the relationship between peer victimization and antisocial behaviour is indeed due to genetic influences. This research is being finalized and will be submitted during the course of 2016.

New avenues: innovative techniques to strengthen causal inference in observational research

The research conducted for this research project demonstrates the importance of taking into account genetic influences when examining the effect of a risk factor on an outcome. New techniques using DNA information are currently being implemented and developed to better estimate the causal role of risk factors in observational research. Mendelian randomization is such a technique: it uses genetic variants, called genetic instruments, that predict a risk factor (e.g. alcohol consumption) to assess the role of this risk factor on an outcome of interest (e.g. antisocial behaviour). These techniques represent a promising avenue to further extend the work that has been conducted for this project. In an article in press in Psychopathology Review, I systematically reviewed all the studies using Mendelian randomization in the field of psychopathology, highlighting the promises and the need for further research in this area.